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The failure modes of biological prosthetic heart valves.

Bioprosthetic heart valves have been used since the 1960s, starting with the use of homograft aortic valves obtained from human cadavers. Today prosthetic heart valves are used widely, and bioprostheses account for close to 40% of all heart-valve replacements. Although most bioprosthesis are still stented porcine aortic valves, the introduction of stentless valves and the increasing use of cryopreserved homograft valves has led to an upsurge of interest in bioprosthesis. There have been significant changes in the handling and fixation of porcine aortic valves; however, their modes of failure remain virtually unchanged, although many bioprosthetic valves now last for considerably longer periods. This article reviews the modes of failure of bioprosthetic heart valves.

Animals↗

Periodate-mediated glycosaminoglycan stabilization in bioprosthetic heart valves.

Bioprosthetic heart valves (BPHVs) derived from glutaraldehyde-crosslinked porcine aortic valves are frequently used in heart valve replacement surgeries. However, the majority of bioprostheses fail clinically because of calcification and degeneration. We have recently shown that glycosaminoglycan (GAG) loss may be in part responsible for degeneration of glutaraldehyde-crosslinked bioprostheses. In the present studies, we used a mild reaction of periodate-mediated crosslinking to stabilize glycosaminoglycans in the bioprosthetic tissue. We demonstrate the feasibility of periodate reaction by crosslinking major components of extracellular matrix of bioprosthetic heart valve tissue, namely type I collagen and hyaluronic acid (HA). Uronic acid assay of periodate-fixed HA-collagen matrices showed 48% of HA disaccharides were bound to collagen. Furthermore, we show that such reactions are also feasible to fix glycosaminoglycans present in the middle spongiosa layer of bioprosthetic heart valves. The periodate reactions were compatible with conventional glutaraldehyde crosslinking and showed adequate stabilization of extracellular matrix as demonstrated by thermal denaturation temperature and collagenase assays. Moreover, uronic acid assays of periodate-fixed BPHV cusps showed 36% reduction in the amount of unbound GAG disaccharides as compared with glutaraldehyde-crosslinked cusps. We also demonstrate that calcification of BPHV cusps was significantly reduced in the periodate-fixed group as compared with the glutaraldehyde-fixed group in 21-day rat subdermal calcification studies (periodate-fixed tissue Ca 72.01 +/- 5.97 microg/mg, glutaraldehyde-fixed tissue Ca 107.25 +/- 6.56 microg/mg). We conclude that periodate-mediated GAG fixation could reduce structural degeneration of BPHVs and may therefore increase the useful lifetime of these devices.

Animals↗

[Using chemical methods to crosslink xenogeneic heart valves: the progress of bioprosthetic heart valves].

Glutaraldehyde clinically is the most commonly accepted crosslinking reagent for bioprosthetic valves preparation. Glutaraldehyde-treated tissue is stable against chemical and enzymatic degradation; however, its calcification and cytotoxicity are severe. Dye-mediated photooxidation is an alternative tissue preservation method that oxidizes the protein with visible light in the presence of a suitable photosensitizer. This article reviews chemical mechanism, research progress, clinical applications future development of these two methods.

Animals↗

Structural integrity assessment of heart valve prostheses: a damage tolerance analysis of the CarboMedics Prosthetic Heart Valve.

The design of mechanical heart valve prostheses must satisfy three basic requirements: biocompatibility, efficiency and durability. Over the past 25 years of clinical use, pyrolytic carbon has proven to be biocompatible and thromboresistant, and is therefore the material of choice for mechanical heart valve prostheses. However, in recent years the material has been questioned in this application because it is brittle and susceptible to subcritical crack growth. This has raised concerns regarding the structural reliability of prostheses constructed from this material. This paper describes the application of the damage tolerance methodology to assess the structural integrity of heart valve prostheses made of pyrolytic carbon. In particular, an analysis of the CarboMedics Prosthetic Heart Valve (CPHV) is presented. A new measure of fatigue lifetime, the fatigue safe-life index, is introduced. Additionally, the degradation of structural integrity from cavitation erosion is examined. It is shown that structural integrity, especially for brittle materials, is not just a function of design, but involves the entire manufacturing process. The damage tolerance method can be applied to assess and ensure the structural integrity of pyrolytic carbon prosthetic heart valve components.

Biocompatible Materials↗

Tricuspid valve replacement: UK Heart Valve Registry mid-term results comparing mechanical and biological prostheses.

BACKGROUND: Little is known of time-related outcome and comparative performance of biological and mechanical prostheses following tricuspid valve replacement (TVR). METHODS: A retrospective UK Heart Valve Registry study (Jan 1, 1986 to June 30, 1997) identified 425 patients who underwent TVR. Two-hundred twenty-five (52.9%) received biological and 200 (47.1%) received mechanical valves. One-hundred sixty (38%), 158, and 76 had isolated, double, and triple valve replacements, respectively. The follow-up was 96% complete with a total of 1,585 patient-years. RESULTS: Thirty-day mortality for TVR was 17.3% (73 deaths). One-, 5-, and 10-year survival rates were 72.2%, 59.9%, and 42.9%, respectively. Year of operation (p = 0.04), age (p = 0.04), and number of valves implanted (p = 0.0 3) predicted overall mortality. Age (p<0.001) and year of operation (p = 0.002) predicted overall survival. Thirty-day mortality for biological and mechanical prostheses was 18.8% and 15.6%, respectively. One-, 5-, and 10-year survival rates were 70.5%, 61.5%, and 47.7% for biological and 74.0%, 57.9%, and 33.9% for mechanical prostheses, respectively. Freedom from reoperation at 1 and 10 years was 98.7% and 97.4%. Freedom from death or reoperation was 71.2% at 1 year and 41.9% at 10 years. None of the above outcomes was significantly different between the type of valve prostheses. CONCLUSIONS: TVR carries a high 30-day mortality and a poor longer term survival. No superiority could be identified for biological or mechanical prostheses in the tricuspid position for either survival or reoperation.

Bioprosthesis↗

The in vitro construction of a tissue engineered bioprosthetic heart valve.

PROBLEM: Heart valve replacement with either a nonliving xenograft or a mechanical prosthesis is an effective therapy for valvular heart disease. Both of these approaches have limitations, including their inability to grow, repair, and remodel. In addition, a mechanical prosthesis requires long-term anticoagulation therapy. METHODS: This study demonstrates the in vitro creation of tissue engineered heart valve tissue using cardiovascular cells on degradable polymer matrices, 40 heart valve leaflets were created using this technique from two sources. Xenograft leaflets were created using human dermal fibroblasts and bovine aortic endothelial cells (n = 20) or allograft valve leaflets were created using sheep myofibroblasts and sheep endothelial cells (n = 20). A mixed sheep cell population was obtained consisting of endothelial cells and myofibroblasts. Endothelial cells were labelled with acethylated low density lipoprotein (Ac-Dil-LDL) and cells were separated into two groups using an activated cell sorter: LDL positive cells comprised of a pure endothelial cell population and LDL negative cells comprised of mixed cell population containing myofibroblasts and smooth muscle cells. The LDL negative cells were seeded on a synthetic polyglycolic acid (PGA) mesh and grown in vitro to form a tissue-like fibroblast-mesh core. Endothelial cells were then seeded onto the surface of the fibroblast-mesh core, forming a single monolayer. RESULTS: Histological evaluation of these constructs revealed an inner core of LDL negative cells and outer endothelial-like cells which were factor VIII positive. There was no evidence of capillary formation from endothelial cells invading the myofibroblasts and smooth muscle matrix and the endothelial lining appeared complete. CONCLUSIONS: It is feasible to construct allogenic heart valve tissue which could be used to make a valve.

Animals↗

Donor valves as substitutes for heart valve replacement.

The main problems of heart valve replacement in Sri Lanka are the cost of prosthetic valves and anticoagulant related complications. The use of human donor heart valves (homografts; allogeneic heart valves [AHV]) will alleviate these shortcomings. Recipients of AHV do not require anticoagulant therapy. Moreover, cryopreservation of AHV offers the opportunity for the storage of valves for an extended length of time with the preservation of valve integrity which is essential for their function after implantation. A donor valve bank can potentially provide diameter matched valves for recipients. Current research suggests that the adverse immunological reactions initiated by AHV cause tissue degeneration in a proportion of these implants. However, the grafts may be improved before implantation during the disinfection and storage of the valves. In this essay an overview on the advantages of using AHV, current concepts of valve banking, recent advances in the understanding of AHV immunogenicity, emerging techniques for immunomodulation of AHV and the possibility of setting up a donor heart valve bank in Sri Lanka are discussed.

Heart Valves↗

Ultrasonic decalcification of calcified valve and annulus during heart valve replacement.

A heavily calcified heart valve annulus increases the likelihood of sequelae after prosthetic valve replacement. Such sequelae include cerebral embolism, paravalvular leakage, valvular dysfunction, rhythm disturbance, hemolysis, communication of the heart chambers, and rupture of the posterior wall of the left ventricle. From January 1991 through June 1994, we performed heart valve replacement on 30 patients, using an ultrasonic surgical aspirator to remove calcific deposits. We placed aortic valve prostheses in 12 patients, mitral valve prostheses in 13 patients, and both aortic and mitral prostheses in 5 patients, after ultrasonic débridement of calcified annuli. All patients were re-examined 6 months after surgery: echocardiographic study showed no paravalvular leakage or valve-related complications. In our experience, ultrasonic decalcification of the annulus is superior to traditional methods. We advocate the use of ultrasonic débridement as an adjunctive tool in calcified heart valve replacement.

Adult↗

Regurgitation of prosthetic heart valves: dependence on heart rate and cardiac output.

Prosthetic heart valves exhibit closure and leakage backflow; however, no well-controlled study to evaluate the influence of factors such as cardiac output and heart rate on backflow has been reported to date. Four clinically used prosthetic aortic valves (size 27 mm)--St. Jude Medical, Björk-Shiley Spherical Disc, Björk-Shiley Convexo Concave, and Starr-Edwards model 1260--were studied in the aortic chamber of a pulse duplication system at heart rates of 50, 80, 110, and 140 beats/min, cardiac output of 2, 4, 6, and 8 liters/min, and mean aortic pressure of 100 mm Hg. Regurgitation was calculated in percentage and found to vary directly with heart rate and inversely with cardiac output. The range of values obtained were 5.5% for the Starr-Edwards model 1260 valve at 110 beats/min and 8 liters/min, to 37.5% for the Björk-Shiley Convexo Concave valve at 140 beats/min and 2 liters/min. Regurgitation was also calculated in milliliters/stroke and ranged from 3.4 ml/stroke for the Starr-Edwards model 1260 valve at 140 beats/min and 2 liters/min, to 17.3 ml/stroke for the Björk-Shiley spherical disc valve at 50 beats/min and 2 liters/min. Regurgitation associated with prosthetic heart valves may present a problem clinically, particularly under conditions of low cardiac output and tachycardia.

Cardiac Output↗

Advances in heart valve surgery.

Heart valve surgery continues to evolve in a dynamic fashion. While the exact role of minimally invasive approaches still needs to be defined, progress has been made in the development of new bioprostheses and their durability. Most importantly, valve repair has been standardized for the mitral and introduced for the aortic valve with results that have been superior to valve replacement. Selection of the optimal procedure for the individual patient is now facilitated. In the future, a wider application of repair procedures and further improvements of biologic valves can be anticipated not only to influence long-term results but also the decision-making process for conservative or surgical treatment.

Aortic Valve↗